Mitapivat

Company has already submitted proposed confirmatory trial for FDA review, as required under accelerated approval pathway Company plans to submit mitapivat sNDA in sickle cell disease in the coming months, and is actively working with FDA to achieve alignment on confirmatory trial required for submission CAMBRIDGE, Mass., March 31, 2026 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, today announced that it will pursue U.S. accelerated approval for mitapivat, an oral pyruvate kinase (PK) activator, in sickle cell disease, following completion of its pre-supplemental New Drug Application (sNDA) meeting with the U.S. Food and Drug Administration (FDA). The purpose of the pre-sNDA meeting was to present the data from the mitapivat RISE UP clinical program in sickle cell disease, including both the Phase 2 and Phase 3 trials. Based on the discussion, the FDA recommended submission of a proposal for a confirmatory clinical trial to support U.S. accelerated approval of mitapivat. The FDA’s accelerated approval pathway expedites the availability of medicines that can fill a medical need for a serious condition, with the requirement of a confirmatory clinical trial to convert to a traditional approval. “Our engagements with the FDA continue to underscore both the unmet need in sickle cell disease and the importance of expeditiously advancing new treatment options for patients living with this complex, debilitating, and deadly disease,” said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. “The clinically meaningful benefits observed in the RISE UP clinical program, combined with our ongoing, constructive, and collaborative dialogue with the FDA, reinforce our confidence in mitapivat’s potential in sickle cell disease. We are focused on advancing mitapivat as rapidly as possible with the rigor required for potential U.S. accelerated approval.” Agios has already submitted its proposal for the required confirmatory clinical trial to the FDA for review. This proposal incorporates a primary endpoint that is different from those in the RISE UP clinical program and is informed by both analyses of RISE UP data and discussions with the FDA. Based on current planning assumptions, the proposed confirmatory clinical trial is not expected to change the company’s previously issued operating expense guidance, which remains approximately flat compared to 2025. The company plans to submit a mitapivat sNDA for sickle cell disease in the coming months, and is actively working with the FDA to achieve alignment on the confirmatory clinical trial required for submission. About Sickle Cell Disease Sickle cell disease is a rare, inherited blood disorder caused by the production of abnormal hemoglobin that disrupts the ability of red blood cells to carry oxygen throughout the body. As a result, red blood cells become rigid and sickle-shaped, causing deformation of red blood cell membranes and the premature death of the cells. These effects lead to chronic hemolytic anemia, vaso-occlusion, and a cascade of severe and life-threatening complications, including long-term damage to the lungs, kidneys, and cardiovascular system. Due to its physical toll, sickle cell disease imposes a profound burden on patients and their families, marked by increased healthcare needs and early mortality. About Mitapivat in Sickle Cell Disease Mitapivat, an oral pyruvate kinase (PK) activator, is designed to enhance the process by which red blood cells produce energy. This approach has the potential to improve red blood cell health by increasing ATP levels to support increased energy demands and lowering levels of a molecule called 2,3-diphosphoglycerate (2,3-DPG). In sickle cell disease, increased stress on red blood cells results in elevated levels of 2,3-DPG, which raises the likelihood that red blood cells develop the abnormal “sickle” shape that triggers vaso-occlusive crises. About the RISE UP Phase 3 Trial Topline Results The global RISE UP Phase 3 trial ( NCT05031780 ) is evaluating the efficacy and safety of mitapivat in sickle cell disease patients aged 16 years or older, representative of the global population. The trial consisted of a 52-week, double-blind, randomized, placebo-controlled phase, in which 207 participants were randomized 2:1 to receive oral mitapivat (100 mg) twice daily (n=138) or matched-placebo (n=69). Upon completion, participants could transition into an open-label extension phase where all receive mitapivat. To comprehensively evaluate objective measures of hemolysis alongside other clinically relevant outcomes in sickle cell disease, the double-blind phase of RISE UP included two primary endpoints – hemoglobin response and annualized rate of sickle cell pain crises – as well as five key secondary endpoints measuring hemoglobin concentration, indirect bilirubin (a biomarker of hemolysis), patient-reported fatigue, hospitalizations for sickle cell pain crises, and percent reticulocyte levels (a biomarker of erythropoiesis). Mitapivat demonstrated a statistically significant improvement compared to placebo in the study’s primary endpoint of hemoglobin response, defined as a ≥1.0 g/dL increase from baseline in average hemoglobin concentration from Week 24 through Week 52. Although mitapivat showed a reduction in the annualized rate of sickle cell pain crises compared with placebo, this primary endpoint did not reach statistical significance. Patients receiving mitapivat who achieved the hemoglobin response primary endpoint had clinically meaningful improvements in hemoglobin concentration. These patients also experienced other clinically meaningful benefits, including reductions in pain crises and related hospital visits, along with improvements in fatigue. The safety pro favorable and consistent with prior mitapivat trials in sickle cell disease. The 52-week double-blind phase was completed by 87.0% (n=120/138) of patients in the mitapivat arm and 81.2% (n=56/69) of patients in the placebo arm. All but two of these patients (174/176) opted to enter the ongoing open-label extension phase of the trial. About Agios: Fueled by Connections to Transform Rare Diseases™ At Agios, our vision is to redefine the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities – collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve. Agios is a commercial-stage biopharmaceutical company headquartered in Cambridge, Massachusetts. To learn more, visit and follow us on LinkedIn and X . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of mitapivat; Agios’ expectations for its submission of a sNDA and the review of such sNDA by the FDA; Agios’ commercial expectations for mitapivat; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts: Investor Contact Morgan Sanford, Vice President, Investor Relations Agios Pharmaceuticals morgan.sanford@agios.com Media Contact Eamonn Nolan, Senior Director, Corporate Communications Agios Pharmaceuticals eamonn.nolan@agios.com

RNA是生命活动里的“隐形指挥家”——它调控着基因表达、病毒复制，甚至是细胞的生老病死，但它的三维结构却像团“会变的毛线”：传统解析方法要么靠碰运气“开盲盒”（不知道哪些序列能形成稳定结构），要么实验成本高到吓人，一直是科学家的“老大难”。现在，AI正在把这个“盲盒”变成“明牌”，连新药研发都跟着踩上了“加速器”。 复旦大学和华西医院的团队最近搞出个“黑科技”：他们把AI和冷冻电镜结合，研发了CRAFTS模型。这模型像个“RNA结构侦探”——从RNAcentral、NCBI里的10亿多条非冗余序列中，用自监督学习提取家族特异的结构特征：同一RNA家族的序列会被“粘”在一起，不同家族的则被“推开”。 比如分析5S rRNA、I类内含子这些经典家族时，AI推荐的序列用冷冻电镜一测，果然结构稳定。以前实验人员要“瞎摸”几个月的活，现在AI几分钟就能给出方向，直接把RNA结构解析的效率拉满，连找小分子药物的靶点都快了——毕竟知道了RNA的结构，就能像“配钥匙”一样找能结合它的分子。 全球的科学家都在AI+RNA赛道上“卷”：香港中文大学、复旦、哈佛的RhoFold+模型，能从序列直接预测单链RNA的3D结构，比传统方法准得多；麻省理工的RhoDesign更绝，能从头设计RNA适配体——就是那种能精准“抓住”靶蛋白的RNA分子，结构相似但序列不同，亲和力还高；Google的AlphaFold3更全能，现在不仅能预测蛋白质结构，连蛋白质-RNA、RNA-小分子的复合物结构都能算，误差不到2Å（相当于原子级别的精准）。 企业也没闲着。国内专注RNA靶向药的ReviR公司，搞了个VoyageR平台——能快速筛选RNA上的“结合口袋”（就是小分子药物能卡住的地方），还能在临床试验前预测靶点是不是真有用。 他们最近挖来了Paul August博士当CSO，这位大佬以前在赛诺菲、Agios搞过不少新药（比如治疗丙酮酸激酶缺乏症的Pyrukynd），现在带着团队瞄准亨廷顿舞蹈症、渐冻症、肿瘤这些“硬骨头”——以前要几年的筛选工作，现在AI几个月就能搞定。 连学术界的会议都把AI+RNA当成“C位”。明年5月，中国生物物理学会要在合肥开第二届RNA治疗学年会，专门设了“AI赋能RNA治疗”议题：讨论AI怎么加速RNA结构预测、靶点筛选，怎么优化递送系统（比如让RNA药更精准到达病灶），还有面临的数据和算法挑战。 除此之外，会议还会聊环状RNA、自扩增RNA这些新型分子，RNA疫苗的创新设计，以及从实验室到临床的转化问题——连产学研合作和青年学者论坛都安排上了，看来这股AI+RNA的风要越刮越猛。 从“开盲盒”到“明牌”，AI正在把RNA从“研究难点”变成“治疗新希望”。以前科学家盯着蛋白质靶点发愁（80%的蛋白质没有可成药靶点），现在沿着中心法则往上走，RNA变成了更大的“靶点库”。 接下来，就看AI能不能把更多RNA的“秘密”挖出来，变成能治病的药——毕竟，生命的答案，可能就藏在这团“会变的毛线”里。